The results of in vitro and in vivo experiments indicated that MLH1, together with low levels of Top1, contributed to colon cancer resistance to irinotecan.
We illustrate the phenomenon using the MethyLight technology, applying our proposed analysis to compare MLH1 DNA methylation levels in males and females studied in the Colon Cancer Family Registry.
We previously identified a novel genomic instability phenotype of multiple reciprocal chromosomal translocations in a MLH1-defective, microsatellite unstable (MSI) colon cancer cell line (HCA7) and, further, showed that it was unlikely to be directly caused by the mismatch repair (MMR) defect in this cell line.
Germ-line hMLH1 mutations are causally associated with inherited MSI colon cancer, and somatic mutations are causally associated with sporadic MSI colon cancer.
In a large-enrollment, sophomore-level laboratory course, groups of three to four students were assigned a gene associated with either breast cancer (brc-1), Wilson disease (cua-1), ovarian dysgenesis (fshr-1), or colon cancer (mlh-1).
Mutations in the mismatch repair (MMR) genes MSH2, MSH6, MLH1 and PMS2 are associated with Lynch Syndrome (LS), a familial predisposition to early-onset cancer of the colon and other organs.
We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer.
The distributions of cancer deaths in 485 individuals from 67 families with LS (35, 30, and two families with MutL homologue 1 (MLH1), MSH2, and MSH6 gene mutations, respectively), obtained from the Registry of the Japanese Society for Cancer of the Colon and Rectum were analyzed.
This retrospective cohort study comprised 79 carriers of germline mutation in a MMR gene (18 MLH1, 55 MSH2, 4 MSH6, and 2 PMS2) from the Colon Cancer Family Registry who had had a proctectomy for index rectal cancer.
A total of 864 tumors from individuals with colon cancer from Utah and Northern California were evaluated by methylation-specific polymerase chain reaction of CpG islands in hMLH1, methylated in tumors (MINT) 1, MINT 2, MINT 31, and CDKN2A (p16).
Colon cancer tissue was assayed using immunohistochemistry for expression of hMLH1 and hMSH2, and a panel of five pairs of microsatellite primers (NR21, NR22, NR24, BAT25, and BAT26) for MSI-H analysis and additional dinucleotide markers (D17S250, D5S346, and D2S123) used for MSI-L.
In this study, we evaluated the frequency of microsatellite instability (MSI) using the five markers suggested by the National Cancer Institute workshop, target gene mutations, hMLH1 and hMSH2 expression, and hMLH1 promoter hypermethylation in the adenomas of patients with and without a SFDR affected by colon cancer.
Treatment of MLH1-methylated colon cancer cell lines with the demethylating agent 5'-aza-2'-deoxycytidine induces the expression of MLH1 and sensitizes cancer cells to 5-fluorouracil.
Members of hereditary nonpolyposis colon cancer (HNPCC) families harboring heterozygous germline mutations in the DNA mismatch repair genes hMSH2 or hMLH1 present with tumors generally two to three decades earlier than individuals with nonfamilial sporadic colon cancer.
Prostate cancers (mean age at diagnosis = 62 ± SD = 8 years) from 32 MMR mutation carriers (23 MSH2, 5 MLH1 and 4 MSH6) enrolled in the Australasian, Mayo Clinic and Ontario sites of the Colon Cancer Family Registry were examined for clinico-pathologic features and MMR-deficiency (immunohistochemical loss of MMR protein expression and high levels of microsatellite instability; MSI-H).